Poxel Announces Completion of Patient Enrollment for TIMES 2 Trial in Phase 3 Registration Program for Imeglimin, an Investigational Therapeutic Agent for Type 2 Diabetes, in Japan

Phase 3 TIMES 1, TIMES 2 and TIMES 3 trials for Imeglimin are now
fully enrolled with over 1,100 patients

Phase 3 TIMES data results are on track for 2019

Japanese New Drug Application submission for Imeglimin targeted in
2020

Diabetes is a fast-growing market in Asia and Japan is the second
largest single market for type 2 diabetes outside of the U.S.; it is
expected to grow to approximately $6 billion in 20201

LYON, France--(BUSINESS WIRE)--
POXEL
SA (Euronext – POXEL - FR0012432516), a biopharmaceutical company
focused on the development of innovative treatments for metabolic
diseases, including type 2 diabetes and non-alcoholic steatohepatitis
(NASH), announced today that patient enrollment has been completed in
the TIMES 2 trial of the Phase 3 registration program for Imeglimin, an
investigational therapeutic agent for type 2 diabetes, in Japan.
Referred to as TIMES (Trials of IMeglimin for Efficacy
and Safety), the Imeglimin Phase 3 registration program in
Japan includes three pivotal trials to evaluate the efficacy and safety
of Imeglimin in over 1,100 patients. The TIMES 2 trial is a 52-week,
open-label, parallel-group study to assess the long-term safety and
efficacy of Imeglimin in Japanese patients with type 2 diabetes. In this
trial, Imeglimin is administrated as a monotherapy or combination
therapy to over 700 patients with existing hypoglycemic agents,
including a DPP4 inhibitor, SGLT2 inhibitor, biguanide, sulphonylurea
and GLP1 receptor agonist.

“In less than one year after signing the strategic partnership with
Sumitomo Dainippon Pharma, we have made substantial progress advancing
all three pivotal Phase 3 TIMES trials for Imeglimin in Japan. This
achievement is a direct result of our close collaboration with Sumitomo
Dainippon Pharma. We remain on track for the TIMES 1 data results in the
second quarter of 2019 and the TIMES 2 and TIMES 3 data results are
anticipated in the second half of 2019,” said Thomas Kuhn, CEO of Poxel.
“In addition to advancing the Imeglimin Phase 3 program in Japan, we
have recently established a subsidiary and expanded our team with the
appointment of Takashi Kaneko, MD, PhD, as Senior Vice President Medical
and President of Poxel Japan K.K.”

“I am very pleased to report that the execution of the TIMES program,
which is being led by Poxel, has continued to progress in a very timely
manner and we have now completed enrollment of all three Phase 3 pivotal
studies, which includes over 1,100 patients,” said Christophe
Arbet-Engels, MD, PhD, Chief Medical Officer, Executive Vice President,
Late Development and Medical Affairs of Poxel. “We are committed to the
successful completion of the TIMES program and will continue to closely
collaborate with our colleagues at Sumitomo Dainippon Pharma to support
the Japanese New Drug Application submission anticipated in 2020. Our
near-term goal in Japan is to provide patients with a new, innovative
therapeutic option for type 2 diabetes.”

The TIMES program is a joint development effort between Poxel and
Sumitomo Dainippon Pharma. The companies entered into a strategic
partnership in October 2017 for the development and commercialization of
Imeglimin in Japan, China, South Korea, Taiwan and nine other Southeast
and East Asian countries.2

Imeglimin is an orally-available drug candidate with a novel mechanism
of action that has been observed in clinical studies to demonstrate
glucose lowering benefits by simultaneously targeting all three key
organs which play an important role in the treatment of type 2 diabetes:
the liver, muscles and the pancreas. Imeglimin has demonstrated in
preclinical studies the potential to address mitochondrial dysfunction,
which is believed to be at the core of type 2 diabetes pathophysiology.
Imeglimin has completed Phase 1 and Phase 2 development in over 1,200
subjects in the U.S., Europe and Japan.

About the TIMES ProgramTIMES (Trials of Imeglimin
for Efficacy and Safety), the Phase 3 program
for Imeglimin for the treatment of type 2 diabetes in Japan, consists of
three pivotal trials involving over 1,100 patients. The TIMES program
includes the following three trials that will be performed using the
dose of 1,000 mg twice daily:

TIMES 1: A Phase 3, 24-week, double-blind placebo-controlled,
randomized, monotherapy study to assess the efficacy, safety and
tolerability of Imeglimin in Japanese patients with type 2 diabetes,
using the change in HbA1c as the primary endpoint. Secondary endpoints
of the trial will include other standard glycemic and non-glycemic
parameters.

TIMES 2: A Phase 3, 52-week, open-label, parallel-group study to assess
the long-term safety and efficacy of Imeglimin in Japanese patients with
type 2 diabetes. In this study, Imeglimin will be administrated orally
as a monotherapy or combination therapy with existing hypoglycemic
agents, including a DPP4 inhibitor, SGLT2 inhibitor, biguanide,
sulphonylurea and GLP1 receptor agonist.

TIMES 3: A Phase 3, 16-week, double-blind, placebo-controlled,
randomized study with a 36-week open-label extension period to evaluate
the efficacy and safety of Imeglimin in combination with insulin in
Japanese patients with type 2 diabetes and inadequate glycemic control
on insulin therapy.

About ImegliminImeglimin is the first clinical candidate in
a new chemical class of oral agents called Glimins by the World Health
Organization. Imeglimin has a unique mechanism of action (“MOA”) that
targets mitochondrial bioenergetics. Imeglimin acts on all three key
organs which play an important role in the treatment of type 2 diabetes:
the liver, muscles and the pancreas, and it has demonstrated glucose
lowering benefits by increasing insulin secretion in response to
glucose, improving insulin sensitivity and suppressing gluconeogenesis.
This MOA has the potential to prevent endothelial and diastolic
dysfunction, which can provide protective effects on micro- and
macro-vascular defects induced by diabetes. It also has the potential
for protective effect on beta-cell survival and function. This unique
MOA offers the potential opportunity for Imeglimin to be a candidate for
the treatment of type 2 diabetes in almost all stages of the current
anti-diabetic treatment paradigm, including monotherapy or as an add-on
to other glucose lowering therapies.

About Poxel SAPoxel uses its development expertise in
metabolism to advance a pipeline of drug candidates focused on the
treatment of metabolic disorders, including type 2 diabetes and
non-alcoholic steatohepatitis (NASH). We have successfully completed the
Phase 2 clinical program for our first-in-class lead product, Imeglimin,
which targets mitochondrial dysfunction, in the U.S., Europe and Japan.
Together, with our partner Sumitomo Dainippon Pharma, we are conducting
the Phase 3 Trials of IMeglimin for Efficacy and Safety (TIMES) program
for the treatment of type 2 diabetes in Japan. Our partner Roivant
Sciences is responsible for Imeglimin’s development and
commercialization in countries outside of Poxel’s partnership with
Sumitomo Dainippon Pharma, including the U.S. and Europe. PXL770, a
first in class direct adenosine monophosphate-activated protein kinase
(AMPK) activator, is advancing into a Phase 2a proof-of-concept program
for the treatment of NASH. PXL770 could also have the potential to treat
additional metabolic diseases. PXL065 (deuterium-stabilized
R-pioglitazone), a mitochondrial pyruvate carrier (MPC), is in Phase 1
and being developed for the treatment of NASH. Poxel also has additional
earlier-stage programs, including deuterated drug candidates for
metabolic, specialty and rare diseases. We intend to generate further
growth through strategic partnerships and pipeline development.
(Euronext: POXEL, www.poxelpharma.com)